Effect and mechanism of auranofin on extrusion and migration of breast cancer cells.

Background: The relationship between cell extrusion and the occurrence of epithelial-mesenchymal transition (EMT) in tumor cells, as well as their metastasis, is inseparable. This research aimed to observe the effect of the thioredoxin reductase (TrxR) inhibitor auranofin on EMT in breast cancer MDA-MB-231 cells and explore whether auranofin can reduce the migratory activity of tumor cells by acting on cancer cell extrusion. Methods: A cancer cell extrusion model was established by reducing the cell growth environment. The impact of auranofin on the viability of MDA-MB-231 cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Microscopic observation revealed changes in the number and relative EMT morphology of extruded cells in MDA-MB-231 cells treated with auranofin for 24 h. Transwell migration and cell scratch assay were performed to assess the migratory activity of MDA-MB-231 cells under varying auranofin concentrations. Western blot analysis was employed to examine the expression levels of EMT-related and migration-related proteins in Auranofin-treated MDA-MB-231 cells. Results: A cancer cell extrusion model was successfully established by manipulating the cell growth environment. The results of CCK-8 assay showed that auranofin could inhibit the viability of MDA-MB-231 cells. Migration assays revealed a concentration-dependent inhibition of MDA-MB-231 cell migration by auranofin. Auranofin could inhibit the migratory activity of MDA-MB-231 cells, and the intensity of inhibition increased with the increase of auranofin concentration. Western blot analysis indicated that auranofin suppressed the expression of EMT-related proteins, reduced the phenomenon of cell extrusion, modulated the EMT process, and decreased the expression of MMP-9 and MMP-2. Conclusions: Auranofin can reverse EMT transformation induced by cell extrusion in MDA-MB-231 breast cancer cells and decrease cell migratory potential. This effect is possibly mediated through the modulation of EMT-associated protein expression, including E-cadherin and vimentin, along with the suppression of migration-associated proteins MMP-9 and MMP-2.